How are substrates recognized by the ubiquitin-mediated proteolytic system?

A necessary step in the degradation of proteins by the ubiquitin system is recognition by the ubiquitin-protein ligases(s). Various structural features of the proteolytic substrate render it susceptible to conjugation with ubiquitin. The N-terminal residue plays a major role in this process, with distinct sites on the ligase(s) recognizing specific types of N-termini. Post-translational modification of some of these residues is required prior to their recognition. A free N terminus is not the only marker; proteins with either free or blocked N termini can be recognized via structural domains that are downstream and distinct from this residue.

[1]  M. Rechsteiner,et al.  Ubiquitin-mediated pathways for intracellular proteolysis. , 1987, Annual review of cell biology.

[2]  A. Varshavsky,et al.  The degradation signal in a short-lived protein , 1989, Cell.

[3]  D. Ecker,et al.  A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. , 1989, Science.

[4]  A. Ciechanover,et al.  Immunochemical analysis of the turnover of ubiquitin-protein conjugates in intact cells. Relationship to the breakdown of abnormal proteins. , 1982, The Journal of biological chemistry.

[5]  A. Ciechanover,et al.  Transfer RNA is required for conjugation of ubiquitin to selective substrates of the ubiquitin- and ATP-dependent proteolytic system. , 1986, The Journal of biological chemistry.

[6]  S. Litwin,et al.  Determination of the rate of hexokinase-glucose dissociation by the isotope-trapping method. , 1974, The Journal of biological chemistry.

[7]  A. Hershko,et al.  The protein substrate binding site of the ubiquitin-protein ligase system. , 1986, The Journal of biological chemistry.

[8]  A. Hershko,et al.  Specificity of binding of NH2-terminal residue of proteins to ubiquitin-protein ligase. Use of amino acid derivatives to characterize specific binding sites. , 1988, The Journal of biological chemistry.

[9]  W. K. Roberts,et al.  Evidence that approximately eighty per cent of the soluble proteins from Ehrlich ascites cells are Nalpha-acetylated. , 1976, The Journal of biological chemistry.

[10]  S. Arfin,et al.  Cotranslational processing and protein turnover in eukaryotic cells. , 1988, Biochemistry.

[11]  A. Hershko.  Ubiquitin-mediated protein degradation. , 1988, The Journal of biological chemistry.

[12]  A. Varshavsky,et al.  In vivo half-life of a protein is a function of its amino-terminal residue. , 1986, Science.

[13]  S. Rogers,et al.  Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. , 1986, Science.

[14]  A. Ciechanover,et al.  Ubiquitin dependence of selective protein degradation demonstrated in the mammalian cell cycle mutant ts85 , 1984, Cell.

[15]  A. Ciechanover,et al.  The ubiquitin pathway for the degradation of intracellular proteins. , 1986, Progress in nucleic acid research and molecular biology.

[16]  A. Ciechanover,et al.  Degradation of proteins with acetylated amino termini by the ubiquitin system , 1989, Science.

[17]  A. Ciechanover,et al.  Role of arginine-tRNA in protein degradation by the ubiquitin pathway , 1987, Nature.

[18]  J. Tobias,et al.  Universality and structure of the N-end rule. , 1989, The Journal of biological chemistry.

[19]  M. Rechsteiner,et al.  The degradation of guanidinated lysozyme in reticulocyte lysate. , 1986, The Journal of biological chemistry.

[20]  I. A. Rose,et al.  Functional heterogeneity of ubiquitin carrier proteins. , 1985, Progress in clinical and biological research.

[21]  B. Hogan,et al.  Rapid degradation of puromycyl peptides in hepatoma cells and reticulocytes , 1974, FEBS letters.

[22]  F Sherman,et al.  Methionine or not methionine at the beginning of a protein , 1985, BioEssays : news and reviews in molecular, cellular and developmental biology.

[23]  A. Varshavsky,et al.  The ubiquitin system: functions and mechanisms , 1985 .